Dr. Douglas D. McAbee


Dr. Douglas D. McAbee


Professor & Biochem Graduate Advisor (1997) 
Biochemistry, Cell Biology, Cell Membranes 

Teaching: Graduate & undergraduate biochemistry 
Contact: douglas.mcabee@csulb.edu
Phone: 562.985.1558 
Office: MLSC-249 


Teaching Interests

CHEM 441A/B, introductory biochemistry lecture courses; CHEM 443, biochemistry laboratory course; CHEM 542, Special Topics in Biochemistry; CHEM 548, cell membranes.


Research Interests

My laboratory is studying transition metal metabolism by the liver, with particular focus on hepatic iron metabolism. Iron is efficiently recycled after erythrocytes are turned over by the reticuloendothelial system. Most retrieved iron is complexed to a variety of iron-transport -scavenging proteins, including the glycoprotein lactoferrin, and delivered to the liver where it is endocytosed by hepatocytes. In hepatocytes, iron is stored indefinitely or packaged with transferrin and exported.

We have focused our work on understanding the hepatic metabolism of lactoferrin. Hepatocyte clearance of plasma Lf regulates (i) lactoferrin's inhibitory effects on myelopoiesis and chylomicron remnant uptake, and (ii) lactoferrin's association with glycated serum proteins. The role lactoferrin plays in normal hepatic iron metabolism and aberrant hepatic iron overload, however, is poorly understood. We have found that hepatocytes endocytose lactoferrin and its bound iron by multiple hepatocyte receptors including the major subunit (RHL-1) of the asialoglycoprotein receptor and by a yet-to-be-identified iron-inducible binding site. Iron-loading reversibly induces the appearance of the second lactoferrin binding site. We are interested in the nature of the iron-induced lactoferrin binding site on hepatocytes. Its appearance is regulated by the iron status of cells, and its iron-dependent expression requires translation but not transcription. We are investigating the nature of this regulation, what factors are required for its expression and down-regulation.

We have also found that the high-affinity interaction of lactoferrin with RHL-1 is carbohydrate-independent. Moreover, lactoferrin binds at or near the carbohydrate-recognition domain of RHL-1 in a Ca2+-dependent manner. This is the first demonstration that the asialoglycoprotein receptor binds to a protein ligand not requiring the presence of terminal Gal or GalNAc sugars. Structure-function studies are underway to understand the nature of this interaction.

Most recently, we have found that loading of hepatocytes with transition metals Fe, Cu, or Zn blocks endocytosis mediated by the asialoglycoprotein receptor. Zn partially inhibits transferrin receptor internalization as well. We are interested in understanding the specific molecular targets of these metals on vesicular transport as well as the broader effects of metal loading on liver stress, necrosis, and apoptosis. 


Recent Publications

McAbee, D.D. 2001 "Lactoferrin" in Wiley Encylopedia of Molecular Medicine, Wiley & Sons, New York (ISBN 0-471-37494-6), pp 1894-1897.

McAbee, D.D., Jiang, X., and Walsh, K.B. 2000 Lactoferrin binding to the rat asialoglycoprotein receptor requires the receptor's lectin properties. Biochem. J. 348:113-117.

McAbee, D.D. and Jiang, X. 1999 Copper and zinc ions differentially block asialoglycoprotein receptor-mediated endocytosis in isolated rat hepatocytes. J. Biol. Chem. 274:14750-14758.

McAbee, D.D., Bennatt, D.J., and Ling, Y.Y. 1998 Isolated rat hepatocytes bind and internalize lactoferrins via the asialoglycoprotein receptor by a galactose-independent mechanism. Adv. Exper. Med. Biol. 443:113-121.

Sitaram, M., Moloney, B, and McAbee, D.D. 1998 Prokaryotic expression of bovine lactoferrin deletion mutants that bind to the Ca2+-dependent lactoferrin receptor on isolated rat hepatocytes. Prot. Expr. Purif.14:229-236.

McAbee, D.D., Ling, Y.Y., and Stich, C. 1998 Iron loading of isolated rat hepatocytes inhibits asialoglycoprotein receptor dynamics and induces formation of rat hepatic lectin-1 (RHL-1) oligomers. Biochem. J.331:719-726.

Bennatt, D.J., Ling, Y.Y., and McAbee, D.D. 1997 Isolated rat hepatocytes bind lactoferrins by the RHL-1 subunit of the asialoglycoprotein receptor in a galactose-independent manner. Biochemistry 36:8367-8376.

Bennatt, D.J., and McAbee, D.D. 1997 Identification and isolation of a 45 kDa calcium-dependent lactoferrin receptor from rat hepatocytes. Biochemistry 36:8359-8366.

Sitaram, M.P., and McAbee, D.D. 1997 Isolated rat hepatocytes bind and endocytose differentially the N- and C-lobes of bovine lactoferrin. Biochem. J. 323:815-822.

McAbee, D.D. and Ling, Y.Y. 1997 Iron loading of cultured adult rat hepatocytes reversibly enhances lactoferrin binding and endocytosis. J. Cell. Physiol. 171:75-86.